The statins comprise natural products (polyketides) from fungi that have a series of strong effects on some of the most important human diseases.
Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR). HMGR is the enzyme responsible for catalyzing the conversion of HMG-CoA to mevalonate, which is an early and rate-limiting step in the cholesterol biosynthetic pathway. Statins are effective lipid lowering agents and thus have been widely used for lowering serum cholesterol levels in the treatment of hypercholesterolemia reducing the risk of heart attacks. Statins also promote bone formation by affecting the expression of the bone morphogenic protein-2 (BMP-2) and this stimulation can have beneficial effects for the treatment of bone fractures and osteoporosis (Mundy et al., Science(1999) 286: 1946–1949; Sugiyama et al., Biochem Biophys Res Commun (2000) 271:688–92). Recently statins have recently also been recognized as a new type of immunomodulator by acting as direct inhibitors of induction of MHC-II expression by INF-γ and thus as repressors of MHC-II-mediated T-cell activation (Kwark et al., Nature Med., (2001) 6: 1399–1402). Naturally occurring statins have antifungal activity (Auclair et al., Bioorganic and Medicinal Chemistry Letters (2001), 11: 1527–1531). Chemically modified statin molecules vary in their retention time in the body, the area of accumulation in the body and effectiveness per dose among other differences (Motti et al., Ann Ital Med Int, 2000, 15: 96–102).
The naturally occurring statins can be subdivided into mevinolins (=monacolins) and compactins. The mevinolins are produced by Aspergillus terreus and Monascus ruber, while Endo et al. (Journal Antibiotics, (1976), 29: 1346–1348) reports the production of compactins by Penicillium citrinum. 
Istvan and Deisenhofer, (Science (2001) 292: 1160–1164) have recently disclosed the presumed mechanism of inhibition of the HMGR by natural and chemically synthesized statins.
Due to pleiotropic effects of statins, their reported side effects (gastrointestinal disorders, skin rashes and headache (U.S. Pat. No. 6,245,800)), and the variation in retention time in the body, and effectiveness per dose, a need still exists for statin molecules with unique and desirable properties such as increased effectiveness, less toxicity, altered retention time or concentration in a particular organ compared to commercially available statins.